Intravascular device and method of manufacture and use

ABSTRACT

An intravascular device and method of constructing an intravascular device. The device has a proximal portion which is stiffer than a distal portion. The device of the present invention may also be advanced through small vessels without the aid of a guidewire although a guidewire may be used when necessary. The device may be manufactured in a number of different ways and a preferred method is to use an expanded PTFE liner at the distal portion and an etched PTFE liner along the proximal portion. The device also has a number of different jacket sections, preferably at least four, with increasing durometer towards the proximal end and a braided section with varying pic along the length.

CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] The present application is a continuation-in-part of applicationSer. No. 09/311,903, filed May 14, 1999, which is a continuation-in-partof application Ser. No. 09/243,578, filed Feb. 3, 1999, which is acontinuation-in-part of application Ser. No. 09/018,214, filed of Feb.3, 1998, the full disclosures of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION

[0002] The present invention relates generally to intravascular devicesand methods. Intravascular devices are used to access various areas ofthe vasculature for a variety of reasons. Such devices are used todeliver and withdraw fluids and to deliver other devices such as stents,angioplasty balloons and thrombolytic devices.

[0003] A specific application of the present invention is for treatingacute arterial ischemia in areas such as the brain. The devices andmethods of the present invention are particularly useful in connectionwith the devices and methods described in U.S. patent application Ser.No. 09/311,903, filed May 14, 1999 by Lewis and Bolduc which describedevices for treating acute ischemia. The invention may, of course, beused in other locations in the body for any other purpose.

SUMMARY OF THE INVENTION

[0004] The present invention is directed to intravascular devices andmethods of construction. As an example of a use of the presentinvention, methods and devices for treating ischemia resulting from thepartial or total obstruction of a blood vessel are described. Usually,the obstructions will be high-grade blockages, e.g., those which resultin greater than 75% flow reduction, but in some instances they may be ofa lower grade, e.g., ulcerated lesions. As used hereinafter, the terms“obstruction,” “occlusion,” and “blockage” will be used generallyinterchangeably and will refer to both total obstructions wheresubstantially all flow through a blood vessel is stopped as well as topartial obstructions where flow through the blood vessel remains,although at a lower rate than if the obstruction were absent.

[0005] Preferred use of the present invention is for the treatment ofpatients suffering from acute stroke resulting from a sudden,catastrophic blockage of a cerebral artery. The invention may also beused to minimize or prevent ischemia during other conditions whichresult in blocked points or segments in the cerebral arterialvasculature, such as iatrogenic occlusion of an artery, e.g., duringneurosurgery, or to relieve vasospasm induced ischemia. The presentinvention, however, will also be useful for treating acute blockages inother portions of the vasculature as well as for treating chronicocclusions in the cerebral, cardiac, peripheral, mesenteric and othervasculature. Optionally, the methods of the present invention may beused to facilitate dissolving or removing the primary obstructionresponsible for the ischemia, e.g., by drug delivery, mechanicalintervention, or the like, while perfusion is maintained to relieve theischemia.

[0006] Methods according to the present invention comprise penetrating aperfusion conduit through the blockage and subsequently pumping anoxygenated medium through the conduit at a rate or pressure sufficientto relieve ischemia downstream from the blockage. The oxygenated mediumis preferably blood taken from the patient being treated. In someinstances, however, it will be possible to use other oxygenated media,such as perfluorocarbons or other synthetic blood substitutes. In apreferred aspect of the present invention, the pumping step comprisesdrawing oxygenated blood from the patient, and pumping the blood backthrough the conduit at a controlled pressure and/or rate, typically apressure within the range from 50 mmHg to 400 mmHg, preferably at a meanarterial pressure in the range from 50 mmHg to 150 mmHg, and at a ratein the range from 30 cc/min to 360 cc/min, usually from 30 cc/min to 240cc/min, and preferably from 30 cc/min to 180 cc/min, for the cerebralvasculature. Usually, pressure and flow rate will both be monitored. Theblood flow system preferably keeps the pressure at or below 400 mmHg,350 mmHg, or 300 mmHg. Pressure is preferably monitored using one ormore pressure sensing element(s) on the catheter which may be disposeddistal and/or proximal to the obstruction where the blood or otheroxygenated medium is being released. Flow rate may easily be monitoredon the pumping unit in a conventional manner or may be monitored by aseparate control unit. Conveniently, the blood may be withdrawn througha sheath which is used for percutaneously introducing the perfusionconduit.

[0007] It will usually be desirable to control the pressure and/or flowrate of the oxygenated medium being delivered distally to the occlusion.Usually, the delivered pressure of the oxygenated medium should bemaintained below the local peak systolic pressure and/or mean arterialblood pressure of the vasculature at a location proximal to theocclusion. It will generally be undesirable to expose the vasculaturedistal to the occlusion to a pressure above that to which it has beenexposed prior to the occlusion. Pressure control of the deliveredoxygenated medium will, of course, depend on the manner in which themedium is being delivered. In instances where the oxygenated medium isblood which is being passively perfused past the occlusion, thedelivered pressure will be limited to well below the inlet pressure,which is typically the local pressure in the artery immediately proximalto the occlusion. Pressure control may be necessary, however, when theoxygenated medium or blood is being actively pumped. In such cases, thepump may have a generally continuous (non-pulsatile) output or in somecases may have a pulsatile output, e.g., being pulsed to mimic coronaryoutput. In the case of a continuous pump output, it is preferred thatthe pressure in the vascular bed immediately distal to the occlusion bemaintained below the mean arterial pressure usually being below 150mmHg, often being below 100 mmHg. In the case of a pulsatile pumpoutput, the peak pressure should be maintained below the peak systolicpressure upstream of the occlusion, typically being below 200 mmHg,usually being below 150 mmHg.

[0008] Pressure control of the oxygenated medium being delivereddownstream of the occlusion is preferably achieved using a digital oranalog feedback control apparatus where the pressure and/or flow outputof the pump is regulated based on a measured pressure and/or flow value.The pressure value may be measured directly or indirectly. For example,the pressure downstream of the occlusion may be measured indirectlythrough the perfusion conduit. A separate pressure lumen may be providedin the perfusion conduit and a pressure measurement transducer locatedat the proximal end of the conduit. Pressure sensed by a distal port ofthe pressure measuring conduit will then be transmitted through theconduit to the transducer. Pressure transducers are a preferred pressuresensor for measuring pressure in the vasculature distal to theocclusion. The pressure sensors may be mounted near the distal tip ofthe perfusion conduit itself or could be mounted on a separate guidewireor other structure which crosses the occlusion with the perfusionconduit. The pressure signals generated by the transducers aretransmitted through electrically conductive elements, such as wires, tothe proximal end of the perfusion conduit where they are connected to apressure monitor connected to or integral with the controller. The pumpoutput can then be controlled based on conventional control algorithms,such as proportional control algorithms, derivative control algorithms,integral control algorithms, or combinations thereof. In one embodimentof the present invention, the pressure sensor is spaced from theperfusion outlets so that fluid flow forces do not affect the pressuremeasurements.

[0009] Actual manipulation of the pressure and/or flow provided by acirculating pump can be effected in a variety of ways. In the case ofcentrifugal pumps, the flow can be measured at the pump output and thepressure can be measured in any of the ways set forth above. Control ofboth the flow rate and the pressure can be achieved by appropriatelychanging the pump speed and downstream flow resistance, where the lattercan be manipulated using a control valve. Suitable flow controlalgorithms are well described in the patent and technical literature.

[0010] Control of peristaltic and other positive displacement pumps isachieved in a slightly different way. Flow volume from a positivedisplacement pump is a linear function of the pump speed and thus may becontrolled simply by varying the pump speed. Pressure output from thepositive displacement pump, in contrast, will be dependent on flowresistance downstream from the pump. In order to provide for control ofthe output pressure from the pump (which is necessary to control thepressure downstream of the occlusion), a pressure control system may beprovided. Typically, the pressure control system may comprise a by-passflow loop from the pump output back to the pump inlet. By thencontrolling the amount of blood output which is by-passed back to theinlet, that pressure can be manipulated. Typically, a flow control valvecan be used to adjust the by-pass flow in order to achieve the targetpressure control point downstream of the obstruction. Suitable flow andpressure control algorithms for positive displacement pumps, such asroller pumps, are well described in the patent and technical literature.

[0011] In addition to controlling pressure and/or flow rates, thesystems of the present invention can provide control for a number ofother parameters, such as partial oxygen pressure (pO2) in the perfusedblood, partial carbon dioxide pressure (pCO2) in the perfused blood, pHin the perfused blood, temperature of the perfused blood, metaboliteconcentrations, and the like. Both pO2 and pCO2 can be controlled usingthe oxygenator in the system, as described in more detail below. The pHcan be controlled by introducing appropriate physiologically acceptablepH modifier(s), such as buffer and bicarbonate solutions and the like.Temperature is controlled by providing appropriate heat exchangecapabilities in the extracorporeal pumping system. The temperature willusually be decreased in order to further inhibit tissue damage from theischemic conditions, but could be elevated for other purposes. Suitablesensors and devices for measuring each of the parameters arecommercially available, and suitable control systems can be provided asseparate analog units or as part of a digital controller for the entiresystem, such as a desk or lap top computer which is specially programmedto handle the monitoring and control functions as described in thisapplication. Concentration and/or physiologic activity of certain formedcellular elements, such as white blood cell or platelets, can beselectively controlled with suitable control systems and devices.

[0012] A particular advantage of the present invention lies in theability to lessen or eliminate reperfusion injury which can result fromthe rapid restoration of full blood flow and pressure to ischemictissue. As described above, the use of thrombolytics and other priortreatments can cause the abrupt removal of an obstruction causing rapidinfusion of blood into the ischemic tissue downstream of the occlusion.It is believed that such rapid restoration of full blood flow andpressure, typically at normal physiologic pressures, can result infurther damage to the leaky capillary beds and dysfunctional blood-brainbarrier which results from the prior ischemic condition.

[0013] The present invention allows for a controlled reperfusion of theischemic tissue where blood can initially be released downstream of theobstruction at relatively low pressures and/or flow rates. That is, itwill be desirable to initiate the flow of blood or other oxygenatedmedium slowly and allow the flow rate and pressure to achieve theirtarget values over time. For example, when actively pumping theoxygenated medium, the pumping rate can be initiated at a very lowlevel, typically less than 30 cc/min, often less than 10 cc/min, andsometimes beginning at essentially no flow and can then be increased ina linear or non-linear manner until reaching the target value. Rates ofincrease can be from 1 cc/min/min to 360 cc/min/min, usually being from5 cc/min/min to 120 cc/min/min. Alternatively, the flow of blood orother oxygenated medium can be regulated based on pressure as mentionedabove. For example, flow can begin with a pressure in the previouslyischemic bed no greater than 10 mmHg, typically from 10 mmHg to 70 mmHg.The pressure can then be gradually increased, typically at a rate in therange from 5-100 mmHg over 2, 8 or even 48 hours. In some instances, itmay be desirable to employ blood or other oxygenated medium that hasbeen superoxygenated, i.e., carrying more oxygen per ml than normallyoxygenated blood.

[0014] While pumping will usually be required to achieve and/or maintainadequate perfusion, in some instances passive perfusion may besufficient. In particular, perfusion of the smaller arteries within thecerebral vasculature can sometimes be provided using a perfusion conduithaving inlet ports or apertures on a proximal portion of the conduit andoutlet ports or apertures on a distal portion of the conduit. By thenpositioning the inlet and outlet ports on the proximal and distal sidesof the obstruction, respectively, the natural pressure differential inthe vasculature will be sufficient to perfuse blood through the conduitlumen past the obstruction. Usually, the inlet ports on the perfusionconduit will be positioned at a location as close to the proximal sideof the occlusion as possible in order to minimize the length ofperfusion lumen through which the blood will have to flow. In someinstances, however, it may be necessary to position the inlet portssufficiently proximal to the occlusion so that they lie in a relativelypatent arterial lumen to supply the necessary blood flow and pressure.The cross-sectional area of the perfusion lumen will be maintained aslarge as possible from the point of the inlet ports to the outlet ports.In this way, flow resistance is minimized and flow rate maximized totake full advantage of the natural pressure differential which exists.

[0015] While perfusion is maintained through the perfusion conduit,treatment of the blood vessel blockage may be effected in a variety ofways. For example, thrombolytic, anticoagulant and/or anti-restenoticagents, such as tissue plasminogen activator (tPA), streptokinase,urokinase, heparin, or the like, may be administered to the patientlocally (usually through the perfusion catheter) or systemically. In apreferred aspect of the present invention, such thrombolytic and/oranticoagulant agents may be administered locally to the arterialblockage, preferably through a lumen in the perfusion catheter itself.Such local administration can be proximal to the thrombus or directlyinto the thrombus, e.g., through side infusion ports which arepositioned within the thrombus while the perfusion port(s) arepositioned distal to the thrombus. Optionally, a portion of the bloodwhich is being perfused could be added back to or otherwise combinedwith thrombolytic and/or anticoagulant agent(s) being administeredthrough the catheter. The addition of blood to certain thrombolyticagents will act to augment the desired thrombolytic activity. Theavailability of the autologous blood being perfused greatly facilitatessuch addition. It would also be possible to deliver the agent(s) throughthe same lumen and distal port(s) as the blood being pumped back throughthe perfusion lumen so that the agents are delivered distally of thecatheter. The latter situation may be used advantageously withneuroprotective agents, vasodilators, antispasmotic drugs, angiogenesispromoters, as well as thrombolytics, anticoagulants, and anti-restenoticagents, and the like. The two approaches, of course, may be combined sothat one or more agents, such as thrombolytic agents, are delivereddirectly into the thrombus while neuroprotective or other agents aredelivered distally to the thrombus. Moreover, such delivery routes canalso be employed simultaneously with systemic delivery of drugs or otheragents to the patient.

[0016] Alternatively or additionally, mechanical interventions may beperformed while the vasculature is being perfused according to thepresent invention. For example, a perfusion conduit may have a very lowprofile and be used as a guide element to introduce an interventionalcatheter, such as an angioplasty catheter, an atherectomy catheter, astent-placement catheter, thrombus dissolution device, or the like.

[0017] The perfusion of the oxygenated medium may be performed for arelatively short time in order to relieve ischemia (which may beadvantageous because of damaged capillaries and/or blood-brain barrier)while other interventional steps are being taken, or may be performedfor a much longer time either in anticipation of other interventionalsteps and/or while other long-term interventions are being performed. Inparticular, when thrombolytic and/or anticoagulant agents are being usedto treat the primary blockage, the perfusion can be continued until theblockage is substantially relieved, typically for at least thirtyminutes, often for four to eight hours, or even 2-3 days. In otherinstances, perfusion can be maintained for much longer periods, e.g.,more than one week, more than two weeks, more than a month, or evenlonger. In some cases, it may even be desirable to maintain perfusionand placement of the perfusion conduit for an extended period of timewith the patient having a portable or implantable pump coupled to theconduit. The pump may also have a reservoir for delivery of therapeuticagents and may be implanted or carried on a belt or the like.

[0018] The ability of the present invention to provide for gradual orcontrolled restoration of physiologic blood perfusion pressures and flowrates is a particular advantage when subsequent interventional stepswould otherwise result in abrupt restoration of blood flow. As describedabove, abrupt restoration of blood flow can cause or contribute toreperfusion injuries. By providing for controlled restoration of bloodflow prior to such interventional steps, the ischemic tissue can beconditioned to tolerate physiologic blood flow rates and pressures priorto full restoration by dissolution or other removal of the occlusion.Such gradual restoration of blood flow from very low levels tophysiologic flow rates can typically be achieved over time periods inthe range from one minute, an hour or even up to 48 hours or longer.Perfusion at controlled pressure and/or flow rate may last typically inthe range of 30 minutes to 2 hours, more typically 30 minutes to 9hours. It will be desirable, for example, to initiate perfusion throughthe perfusion conduits of the present invention at mean arterialpressures downstream of the occlusion which are no greater than 25-50%of normal with typical pressures being 20-40 mmHg. The blood flow rateswhich correspond to such pressures will depend largely on the nature ofthe vasculature into which the blood is being perfused and may be lessthan 200 ml/min, less than 150 ml/min and even less than 100 ml/min.

[0019] In addition to delivering oxygen to the ischemic region distal tothe primary occlusion, the blood or other oxygenated medium may carryother treatment agents, including thrombolytic agents, anticoagulantagents, tissue preservative agents, and the like. Moreover, in order tofurther preserve the cerebral tissue distal to the blockage, theoxygenated medium may be cooled to below body temperature, e.g., to atemperature in the range from 2° C. to 36° C., typically from 25° C. to36° C., in order to cool and preserve the tissue. Cooling may beeffected externally as part of the extracorporeal pumping system and/ormay be effected using a thermoelectric or Joule-Thomson expansion cooleron the catheter itself.

[0020] Patients suffering from ischemia resulting from acute or chronicocclusion in the cerebral vasculature may be treated according to thepreferred methods described below. A perfusion conduit is introduced tothe patient's vasculature, and a distal port on the conduit is guidedthrough the occlusion in the cerebral vasculature. Blood, optionallyoxygenated and/or superoxygenated, is obtained from the patient andperfused back to the patient through the distal port on the conduit pastthe occlusion at a rate sufficient to relieve the ischemia. Theoxygenated blood may be arterial blood which may be returned to thepatient without further oxygenation. Alternatively, arterial or venousblood can be oxygenated in suitable apparatus external to the patientand returned to the patient. External oxygenation allows the blood to be“superoxygenated,” i.e., oxygenated at higher levels than would normallybe available from arterial blood. Usually, the method further comprisesdelivering a therapeutic agent to the patient while the perfusing stepis continued, usually being a thrombolytic agent which is deliveredthrough the conduit directly to the vascular occlusion. The occlusion isusually in either a carotid artery, vertebral artery, proximalsubclavian artery, brachiocephalic artery, or an intracerebral artery,and the conduit is usually introduced via the femoral artery in aconventional intravascular approach, typically being positioned over aguidewire which is first used to cross the occlusion. Alternatively, theconduit may be introduced through the axillary or brachial arteries,also in a conventional manner. The conduit may also be advanced throughthe vasculature and through the occlusion without the aid of a guidewireas will be discussed below.

[0021] Apparatus according to the present invention comprisesperfusion/infusion catheters which include a catheter body having aproximal end and a distal end. The catheter body has at least aperfusion lumen and may have other lumens. The catheter may be taperedor may have a constant cross-sectional shape. The catheter may be formedas a single, multi-lumen or single-lumen extrusion or the lumens may beformed as separate tubes. When formed as separate tubes, the tubes maybe fixed relative to each other or may be provided with appropriatesliding seals to permit them to slide relative to each other. Additionallumens and/or tubes may also be provided for purposes discussed in moredetail below. Often, although not always, the catheters will be freefrom external dilatation balloons or other external structure whichcould complicate penetration of the distal end of the catheter throughan obstruction.

[0022] A first embodiment of the catheter is characterized by a largediameter proximal section and a small diameter distal section, where atleast two isolated lumens extend from the proximal end of the catheterbody through both sections to near the distal end of the catheter body.One of the lumens will extend entirely through the catheter body andusually have side ports over a distal length thereof. The other lumenwill usually terminate some distance proximal of the distal tip of thecatheter body and will also usually have side ports over a distal lengththereof. The proximal section has an outer diameter in the range from 1mm to 3 mm, usually from 1.5 mm to 2.5 mm, and typically from 1.5 mm to2 mm, and the distal section has an outer diameter in the range from 0.5mm to 2 mm, preferably from 0.5 mm to 1.5 mm. The first isolated lumenwhich extends entirely through the catheter body will usually betapered, i.e., have a larger diameter over a proximal length thereofthan over a distal length thereof. Usually, the first isolated lumenwill have an inner diameter in the range from 0.75 mm to 1.25 mm in theproximal section, more usually being from 0.9 mm to 1.1 mm in theproximal section, and an inner diameter in the range from 0.25 mm to 1mm in the distal section, usually being from 0.3 mm to 0.75 mm in thedistal section. The second isolated lumen will usually be disposedannularly about the first isolated lumen and will have an inner diameterin the range from 0.9 mm to 2.9 mm in the proximal section, usually from1.4 mm to 1.9 mm in the proximal section, and an inner diameter in therange from 0.4 mm to 1.9 mm in the distal section, usually in the rangefrom 0.5 mm to 1.5 mm in the distal section. The second, outer annularlumen will typically terminate from 5 cm to 25 cm from the distal end ofthe catheter body.

[0023] The catheter may also have a larger flow conduit for achievinghigher flow rates. For example, the inner diameter of the first lumenmay be 1.5-3.0 mm in the proximal section and 1.0-2.0 mm in the distalsection. The second lumen has an inner diameter which is preferably0.25-1.0 mm larger than the outer diameter of the first lumen. The wallthickness of the first lumen is preferably between 0.07-0.20 mm. If thecatheter has a straight instead of tapered configuration the innerdiameter of the first lumen is preferably 1.5-2.5 mm.

[0024] The catheter of the present invention may, of course, have anyother suitable tapered shape or may have a constant cross-sectionalprofile. For example, in another preferred embodiment, the firstcatheter has the perfusion lumen, and in a specific embodiment no otherfluid lumens. Such a catheter has a small, flexible construction whichcan be passed through tortuous vessels. Other catheters may be advancedover the perfusion catheter to remove or displace the obstruction asdiscussed below. The catheters may be another fluid perfusion catheterfor delivery of thrombolytic agents or may be an obstruction removalcatheter which removes the obstruction with mechanical action or with anultrasound transducer, RF electrode or a laser.

[0025] In another aspect of the present invention, the perfusion conduitis advanced through the cerebral vasculature to the obstruction and anobstruction removal catheter is advanced through the perfusion lumen toremove the obstruction. Thus, the perfusion conduit acts as a fluidconduit and/or a guide catheter for reaching distal regions of thecerebral vasculature. The system of the present invention permits theintroduction of catheters through the perfusion lumen to regions asdistal as the middle cerebral artery M1 and M2 segments, anteriorcerebral artery A1 and A2 segments, and the basilar artery or othersimilarly sized vessels which are typically accessed with guidewires.The obstruction removal catheter may be a balloon, stent, perfusion, RF,ultrasound, laser or mechanical atherectomy catheter for removing theobstruction. As will be discussed below, the catheters of the presentinvention may also be advanced without the aid of a guidewire.

[0026] The present invention is also directed to a system having aballoon catheter and an infusion catheter. The balloon catheter has atleast one lumen extending therethrough. The second catheter has a guidetip and fluid infusion openings in a distal region. Both catheters havea proximal region which has a cross-sectional area greater than thedistal region. The second catheter is slidably received in the firstcatheter so that the guide tip and the fluid infusion openings canextend distally from the first catheter.

[0027] In another method of the present invention, a method ofperforming balloon displacement of an obstruction in a patient'svasculature is provided. A balloon catheter is guided over a guidewireto a site in a patient's vasculature. The guidewire is then removed. Aninfusion catheter is then introduced through the balloon catheter. Theinfusion catheter is advanced through the balloon catheter so that thetip extends beyond the balloon catheter. An infusate is then deliveredthrough the infusion catheter.

[0028] In still another aspect of the present invention, a ballooncatheter is provided which is configured to be guided through theperfusion catheter. The balloon catheter has no guidewire lumen and noother structure to track over a guidewire thereby reducing the size ofthe catheter. The distal end of the balloon catheter preferably has asmooth, rounded tip to penetrate the obstruction if necessary. Theballoon catheter may have a tapered shape similar to the perfusioncatheter.

[0029] The devices of the present invention may be manufactured in anysuitable manner. In another aspect of the invention, a preferred methodof constructing the devices described above is to position a liner overa mandrel and wind a reinforcing layer over the liner. A jacket is thenpositioned over the liner and a shrink tube is positioned over thejacket. The entire structure is then heated to fuse the jacket to theliner.

[0030] The device preferably has a flexible distal portion to navigatesmall and tortuous vessels and a stiff proximal portion to providecolumn strength for advancing the device through the vascular system.The distal portion of the liner is preferably made of expanded PTFEwhich provides flexibility. The proximal portion of the liner ispreferably made of etched PTFE so that the proximal portion has greaterstiffness and column strength. An end of the expanded PTFE liner iseverted to form a soft, atraumatic distal end.

[0031] In a preferred embodiment, the jacket has a number of sections,preferably about five. The jacket preferably has increasing stiffnessdistally. The flexural modulus of the jacket preferably increases atleast 25, more preferably at least 40 times, and most preferably about55 times from a distal section to a proximal section. Specifically, thejacket flexural modulus increases from 2000 psi at a distal section to110,000 at a proximal section. The jacket sections also preferablyincreases in durometer towards the proximal end. The jacket preferablyincreases at least 13 D, more preferably at least 25 D, over a distanceof no more than 10 cm, more preferably no more than 8 cm, for threesuccessive sections. The jacket may also have a fourth section with thefirst section being at least 25 D less than the fourth section and thefirst and fourth sections separated by 15 cm or less, more preferably 10cm or less. The jacket may also have a fifth section with the firstsection having a durometer which is at least 28 D less than the fifthsection. The first section is preferably separated from the fifthsection by 20 cm or less and preferably 15 cm or less. The jacket mayeven have a sixth section with the first section having a durometerwhich is at least 40 D less than the sixth section. The first and sixthsections are separated by at least 25 cm or even 20 cm.

[0032] The reinforcing layer also has a number of sections with thedistal section being coil and the proximal sections being braided wire.The braided wire has four sections with decreasing pics toward theproximal end. The first section has a pic which is at least 20 more thanthe third section. The first section is preferably separated from thefirst section by no more than 15 cm and preferably no more than 10 cm.The reinforcing layer may also have a fourth section with the firstsection having a pic which is at least 30 pics more than the fourthsection. The first section is separated from the fourth section by nomore than 20 cm and more preferably no more than 15 cm.

[0033] The catheter of the present invention has a large change instiffness between the proximal and distal sections. Specifically, theproximal section is at least 20, 40, 60 or even 75 times stiffer thanthe distal portion of the catheter. The distal portion preferablyextends at least 10 or even 15 cm from the distal end while the proximalportion extends to within 40, 35 and most preferably to within 30 cmfrom the distal end or closer. The high change in stiffness permits theproximal portion to be rigid enough to prevent buckling and kinkingwhile the distal portion is flexible to pass through tortuous vessels.Although the distal portion is relatively flexible, the distal portionstill retains a relatively large column strength so that the distal endmay be advanced through the vasculature without the aid of a guidewire.A guidewire may, of course, be used at times when needed.

[0034] Apparatus according to the present invention further comprisesystems including a perfusion/infusion catheter as set forth above incombination with a sheath for percutaneously introducing theperfusion/infusion catheter and a pump for receiving blood from thesheath and delivering blood back to the catheter. Optionally, aninfusion device may be provided in the system for infusing a drug to alumen of the perfusion/infusion catheter. Preferably, the systems willinclude control apparatus for controlling blood infusion pressures,blood infusion flow rates, pO2, pCO2, pH, temperature, and/or otherparameters of the blood/oxygenated medium being perfused back to thepatient. The present invention still further comprises kits, including aperfusion catheter and instructions for use setting forth a method forpenetrating the catheter through a blockage in a patient's vasculatureand thereafter perfusing an oxygenated medium through the conduit torelieve ischemia. Kits will usually further comprise a container, suchas a pouch, tray, box, tube, or the like, which contains the catheter aswell as the instructions for use. Optionally, the instructions for useset forth on a separate instructional sheet within the package, butalternatively could be printed in whole or in part on the packagingitself. Optionally, other system components useful for performing themethods of the present invention could be provided within the kit,including guidewires, introductory sheaths, guiding catheters, and thelike.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035] FIGS. 1A-1C illustrate an exemplary protocol for treating a totalocclusion in a blood vessel according to the method of the presentinvention.

[0036]FIG. 2 illustrates an exemplary system for treating a totalocclusion within a patient's cerebral vasculature according to thepresent invention.

[0037]FIG. 3 is a cross-sectional view taken along line 3-3 of FIG. 2.

[0038]FIG. 4 is a cross-sectional view taken along line 4-4 of FIG. 2.

[0039]FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 2.

[0040]FIG. 6 is a cross-sectional view taken along line 6-6 of FIG. 2.

[0041]FIG. 7 illustrates a protocol using the system of FIG. 2 fortreating a cerebral occlusion according to the present invention.

[0042]FIG. 8 is a detailed view of the catheter used for treating theocclusion in the protocol of FIG. 7.

[0043]FIG. 9 illustrates a kit including components according to thepresent invention.

[0044]FIG. 10 illustrates an alternative embodiment of a perfusionconduit constructed in accordance with the principles of the presentinvention.

[0045]FIG. 11 illustrates yet a further embodiment of a perfusionconduit constructed in accordance with the principles of the presentinvention.

[0046]FIG. 12 illustrates yet another exemplary embodiment of aperfusion conduit constructed in accordance with the principles of thepresent invention.

[0047]FIG. 13 illustrates another perfusion catheter with a secondcatheter advanced over the perfusion catheter.

[0048]FIG. 14 illustrates a perfusion used in connection with thecatheters of FIG. 13.

[0049]FIG. 15 illustrates another perfusion catheter having a ballooninflated by fluid infused through the fluid lumen;

[0050]FIG. 16 illustrates a still another perfusion catheter having aballoon with an inflation lumen.

[0051]FIG. 17 illustrates a perfusion catheter with a stent deliverycatheter advanced over the perfusion catheter.

[0052]FIG. 18 illustrates a perfusion catheter with a balloon catheteradvanced over the perfusion catheter.

[0053]FIG. 19 shows another system for treating a cerebral obstruction.

[0054]FIG. 20 shows a balloon catheter displacing an obstruction in acerebral artery.

[0055]FIG. 21 shows another balloon catheter having a second lumen.

[0056]FIG. 22 shows a stent displacing an obstruction in a cerebralartery.

[0057]FIG. 23 shows a perfusion catheter for removing the obstruction.

[0058]FIG. 24 shows another system for treating a cerebral obstructionhaving first and second tapered catheters.

[0059]FIG. 25 is an enlarged view of the distal end of the catheters ofFIG. 23.

[0060]FIG. 26 is a cross-sectional view of the distal end of thecatheters of FIGS. 23 and 24 with a lumen in a relaxed state;

[0061]FIG. 27 is a cross-sectional view of the catheters of FIG. 23 withthe lumen expanded.

[0062]FIG. 28 is shows the system of FIG. 24 with an alternative secondcatheter having an expandable lumen.

[0063]FIG. 29 shows the catheter of FIG. 29 having an expandablesidewall in a collapsed condition.

[0064]FIG. 30 shows the expandable sidewall in an expanded position.

[0065]FIG. 31 is an exploded view showing a method of constructing aninterventional device.

[0066]FIG. 32 is a cross-sectional view showing the method ofconstructing the interventional device of FIG. 31.

[0067]FIG. 33 is a cross-sectional view of the device of FIG. 32 afterheating to fuse the layers together to form an integrated device.

[0068]FIG. 34 shows the distal end of the device with the liner havingan inverted portion at the distal end.

[0069]FIG. 35 is a cross-sectional view of another device.

[0070]FIG. 36 is another cross-sectional view of the device of FIG. 35.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

[0071] The intravascular devices and methods of construction and use aredescribed below. The present invention is described in connection withtreating partial or total occlusions but may be used for any othersuitable purpose. The general principles for treating partial and totalocclusions within a patient's vasculature are described in connectionwith FIGS. 1A-1C. A blood vessel BV which is usually an artery, moreusually a cerebral artery, such as a carotid artery, vertebral artery,or an intracerebral artery, is obstructed by a total occlusion TO. Theocclusion may result from thrombosis at a pre-existing atheroscleroticlesion or may result from the shedding of an embolus from an arterywhich flows distally to the particular vessel in which the occlusionoccurs. Usually, the occlusion will occur abruptly and the sudden lossof perfusion through the blood vessel distal to the total occlusion TOwill place the patient at great risk of neuron death. As discussed abovein the Background section, it is usually necessary to reestablishperfusion within a matter of hours in order to avoid significant tissuedamage or death, particularly in the case of strokes. While six hours isoften considered a maximum delay, earlier treatment is much moredesirable.

[0072] The present invention provides a method for very quicklyreestablishing perfusion through the total occlusion TO in a controlledmanner. Such perfusion is established using a perfusion conduit 10 (FIG.1C) through which oxygenated blood or an oxygenated synthetic medium,such as a perfluorocarbon oxygen carrier, is actively pumped backthrough a lumen of the catheter from a source 12. Usually, the conduitwill include side perfusion ports 14 near its distal end 16 in order toless traumatically disperse the perfused fluid. Optionally, proximalportions of the conduit 10 (not shown) may have enlarged lumen diametersin order to reduce flow resistance and shear forces to further reduce orprevent hemolysis. It will be appreciated that while the distal portionof the conduit 10 will usually have a relatively low profile to accesssmall diameter blood vessels, the proximal portions can be madesignificantly larger to improve the hemodynamic flow and handlingcharacteristics and reduce hemolysis.

[0073] Optionally, the conduit 10 will be introduced over a conventionalguidewire GW which may be initially used to cross the total occlusionTO, as shown in FIG. 1B. In other instances, however, the perfusionconduit 10 may be adapted so that it is able to cross the totalocclusion TO without the use of a conventional guidewire. In some cases,the perfusion conduit may be in the form of a guidewire, e.g., a taperedguidewire, which is suitable for both guiding through the vasculature tothe site of the total or partial occlusion as well as crossing theocclusion.

[0074] The perfusion conduit 10 may be introduced from any normalintravascular introduction site, e.g., through the femoral artery usingthe Seldinger technique. Alternatively, the infusion conduit can beintroduced through the axillary and other arteries.

[0075] A system 20 suitable for treating occlusions within the cerebralvasculature is illustrated in FIGS. 2-6. The system 20 includes aperfusion conduit in the form of intravascular catheter 22. The catheter22 comprises a catheter body 24 having a distal end 26 and a proximalend 28. The catheter body 24 comprises a pair of coaxial tubularelements, including an outer tube 30 and an inner tube 32. Proximal hub34 comprises a first port 36 which is fluidly coupled to an interiorlumen of the inner tube 32 and a second port 38 which is fluidly coupledto an annular lumen between the exterior surface of outer tube 32 andthe interior of tube 30. Proximal port 40 (typically a hemostasis valve)also communicates with the lumen of the inner tubular member 32 and issuitable for intravascular positioning of the catheter 22 over aguidewire.

[0076] The system usually further includes a guiding catheter 50 havingdimensions and characteristics suitable for introducing the catheter 22to the desired intravascular target site. Although illustrated as havinga straight configuration, the guiding catheter 50 will often have apreformed, curved tip selected specifically to reach the intravasculartarget site, and the guiding catheter could further be reinforced (e.g.,braided), have a variable stiffness over its length, have a variablediameter, or the like. The system 20 will usually still further comprisea sheath 60 which is used to percutaneously access the vasculature atthe introductory site, e.g., in the femoral artery. The sheath 60 has aproximal hub 61 including at least one side arm 62. The hub 61 receivesthe catheter 22 therethrough and will include a mechanism formaintaining hemostasis about the catheter. The side arm 62 permitswithdrawal of blood for oxygenation and return to the patient accordingto the present invention. Other side arm(s) may be provided for removalof blood (optionally combined with drugs being delivered back to thepatient), for infusing agents through the sheath 60, or for otherpurposes. Entry of blood into the lumen of the sheath is optionallyfacilitated by side ports 64 formed over at least a distal portion ofthe sheath. The catheter body 24 is tapered in the distal direction,i.e., the diameter is larger near the proximal end 28 than at the distalend 26. As illustrated in FIGS. 2-6, the outer tube 30 has a largediameter proximal section (observed in FIG. 3) and a smaller diameterdistal section (observed in FIGS. 4 and 5). Similarly, the inner tube 32has a large diameter proximal section (shown in FIG. 3) and a smallerdiameter distal section (shown in FIGS. 4-6). The particular outerdiameters and inner lumen diameters of both the outer tube 30 and innertube 32 are within the ranges set forth above. Since the distal terminiiof the outer tube 30 and inner tube 32 are staggered, the catheter body24 is tapered in three stages, with a first diameter reduction occurringat location 33 (FIG. 2) where the diameter of the outer tubular member30 is reduced from the diameter shown in FIG. 3 to the diameter shown inFIG. 4. The second diameter reduction occurs at location 35 where theouter tubular member 30 terminates, leaving the outer surface of theinner tubular member 32 to define the catheter body.

[0077] Such tapered configurations are preferred since they maximize thecross-sectional area of the flow lumens over the length of the catheterto reduce flow resistance for both the blood (or other oxygenatedmedium) and the drug to be delivered. As can be seen in FIG. 3, lumen 70of the inner tubular member 32 which carries the blood is maximizeduntil the diameter is reduced near the distal end of the catheter, asshown in FIG. 4. Similarly, the annular lumen 72 which carries the drugis maximized over the proximal portion before it is reduced after thetransition at location 33. Maintaining the larger diameters and lumenareas is desirable in order to decrease flow resistance and shear forcesto reduce or eliminate hemolysis as the blood is introduced through theentire catheter length. Similarly, a reduction in flow resistance to thedrug being introduced facilitates drug delivery during the procedure.

[0078] Side wall penetrations 80 are provided in a distal portion 26 ofthe outer tubular member 30, as best seen in FIGS. 2 and 5. Thepenetrations 80 will be useful for delivering a therapeutic agentthrough port 38 in order to treat the primary occlusion, as described inmore detail hereinafter.

[0079] Similarly, ports 90 may be formed over at least a distal portionof the inner tubular member 32 which extends beyond the distal end ofthe outer tubular member 30. The penetrations 90 will be available torelease blood or other oxygenated medium that is being perfused back tothe patient through port 36 and the continuous lumen of the tube 32.Note that while the lumen 70 of tube 32 will be available forintroduction of the catheter 22 over a guidewire, the guidewire may beat least partially withdrawn from the lumen 70 in order to furtherdecrease blood flow resistance as it is perfused back to the patient.

[0080] Optionally, the catheter 22 may comprise at least one pressuresensing element 96 disposed at a location near where the blood or otheroxygenated medium is returned to the blood vessel. Preferably, thepressure sensing element 96 may be a piezoelectric or other solid statepressure sensing device and will be connected through the hub 34 by apair of wires 97 which may be connected to conventional electronicdevices for measuring pressure. Thus, pressure may be measured and usedfor controlling rate and/or pressure of blood or other oxygenated mediumpumped back to the patient using conventional analog or digital controlcircuitry. A pressure control point will be selected, usually within theranges set forth above, and the rate or pressure of oxygenated mediumbeing pumped back through the catheter 22 will be controlled to maintainthe control point. Conventional control algorithms, such asproportional, derivative, integral, and combinations thereof, may beemployed for maintaining the desired control point.

[0081] In some instances, it will be desirable to provide at least asecond pressure sensing element 98 which will be located proximal to theobstruction when the catheter is in use. For example, the pressuresensing element 98 may be near the location 35 where the outer tubularmember 30 terminates. The sensor 98 will permit monitoring of thepressure in the vasculature proximal of the occlusion, which pressurewill usually approximate that of the vasculature in the region of theocclusion prior to an acute occlusion event. This pressure, in turn, maybe utilized as a target pressure for the blood or other oxygenatedmedium which is being perfused distal to the occlusion. That is, it maybe desirable to treat the measured “background” pressure as a maximumdesirable pressure for perfusion in order to prevent injury to thevasculature distal to the occlusion.

[0082] Referring now to FIG. 7, use of the system 20 for treating thecerebral vasculature of a patient P will be described. Access to thetarget cerebral artery is established using the sheath 60 in aconventional manner. The guiding catheter 50 is then introduced throughthe sheath 60 and establishes a protected access lumen to a locationwithin the cerebral vasculature. The catheter 22 is then introducedthrough the guiding catheter to the target site within the cerebralvasculature, typically over a guidewire (not illustrated). Conveniently,the catheters will be partly radiopaque and/or radiopaque markers 92(FIG. 2) will be provided at the distal tip of the catheter as well ason either side of the drug ports 80 so that the catheter 22 may beproperly positioned under fluoroscopic guidance relative to theobstruction being treated. After the tip 26 of the catheter 22 ispenetrated through the occlusion TO (FIG. 8) the penetrations 80 arepreferably located within the occlusive material in order to deliver thethrombolytic or other agent to the material. The distal portion of thecatheter, including ports 90, in contrast, are located beyond theocclusive material in order to provide the desired blood perfusion.Blood flow is immediately established using an external pump 100 whichreceives blood from the port 62 of access sheath 60 and returns theoxygenated blood to the catheter 22 through port 36. Any suitabletherapeutic agent, such as a thrombolytic agent, may be introducedthrough port 38 from a source 102. Any other suitable drugs may also bedelivered from the source 102 and through the port 38. Optionally, theblood may be cooled before, during, or after it has passed through thepump unit 100. Still further optionally, the blood may be oxygenated orsuperoxygenated using an oxygen-saturated bubble chamber or conventionalcardiopulmonary bypass oxygenators ORS. In some instances, it may bedesirable to combine the thrombolytic agent with a portion of therecirculating blood before infusing the thrombolytic agent/blood backthrough the port 38.

[0083] Optionally, the pump unit 100 may be controlled by an analog ordigital control unit 110 (FIG. 7). The control unit 110 will receivevarious input control parameters 112, typically including at leastoxygenated medium flow rate and pressure. Other control parameters, suchas pO2, pCO2, pH, temperature, and the like, may also be input into thecontrol unit 110. In turn, the control unit will provide a controloutput 114, typically at least to the pump unit 100 to control outputflow and pressure, as described above. If control of other parameters isdesirable, other capabilities may be added, such as the ability tocontrol the degree of oxygenation in the medium supplied by source 102,the ability to add pH modifiers, such as buffers, bicarbonate, and thelike, to the oxygenated medium, the ability to control a heat exchangerlocated in the blood flow circuit, and the like. The source 102 mayprovide any of the various drugs or therapeutic agents described hereinfor delivery through the ports.

[0084] Kits according to the present invention are illustrated in FIG.9. The kit will include a perfusion conduit, such as perfusion conduit10, as well as instructions for use 120. The catheter and instructionsfor use will usually be combined within a suitable container, such as apouch, tray, box, tube, or the like. The catheter and possibly othercomponents of the system (such as guide catheters, sheaths, thrombolyticor other therapeutic agents, disposable cartridges for pump/oxygenationsystems, or the like) will optionally be included and/or sterilizedwithin the packaging. The instructions for use may be on a separatesheet of paper or may be printed in whole or in part on the packagingmaterials. The instructions will set forth a method of using the devicesin any manner described herein. Furthermore, the kit may include anygrouping of instruments described herein without departing from thescope of the invention.

[0085] Referring now to FIG. 10, a perfusion conduit 200 includes aninner tube 202 and outer tube 204. The inner tube has perfusion ports206 formed in its side wall over a portion of the distal end, and theouter tube 204 has perfusion ports 208 formed over a portion of itsdistal end. The perfusion conduit 200 differs from catheter 22 primarilyin that the inner tubular member 202 is able to slide axially relativeto the outer tubular member 204. A sliding seal 210, typically an O-ringor similar passive seal, is provided to maintain pressure within thelumen of outer tubular member 204 so that thrombolytic and other drugscan be delivered without excessive loss through the distal tip. Someloss of the agent, however, will usually be acceptable so that the sealneed not be completely tight. If a more positive seal is desired, aninflatable balloon 211 (shown in broken line) may be provided inaddition to or in place of the sliding seal 210. Use of the balloon 211is advantageous in that it permits higher infusion pressures withoutleakage from the distal end of the outer tube 204, but disadvantageousin that it limits the range of axial placement of the outer tube 204relative to the inner tube 202. Use of the inner tube 202 for perfusingblood or other oxygenated medium therethrough will generally be asdescribed with the prior embodiments. Radiopaque markers 212 and 214 onthe inner tube 202 will be positioned distally of the occlusion toassure that the perfusion ports 206 will release the delivered bloodwith minimal resistance. Radiopaque markers 216 and 218 on outer tube208, in contrast, will be positioned so that the infusion ports 208 liegenerally within the occluded region. Optionally, the balloon 212 willbe inflated to both lock the inner and outer tubes relative to eachother and to provide a positive seal at the distal end of the outertube, and the thrombolytic or other therapeutic agent will then bedelivered through the lumen of the outer tube into the occlusivematerial, such as thrombus.

[0086] Referring now to FIG. 11, a perfusion conduit 300 also includesan inner tube 302 and an outer tube 304. The inner and outer tubes areslideable relative to each other, and a sliding seal 310 is provided atthe distal end of the outer tube 304. The perfusion conduit 300, incontrast to prior embodiments, is not intended to deliver a therapeuticagent. Instead, it is intended only to perfuse blood or other oxygenatedmedium therethrough. The lumen 312 within the outer tube 304 is intendedfor passing the blood or other oxygenated medium to near the distal endof the conduit 300. The inner tube 302 then receives the blood or otheroxygenated medium through ports 314 which permit the medium to flow fromlumen 312 into the interior lumen of the tube 302. An enlarged portion316 of the tube 302 is provided in order to prevent axial advancement ofthe tube so that the ports 314 cannot extend outside of the outer tube304. Alternatively or additionally, an inflatable balloon 316 may beprovided in order to both prevent excess axial advancement of the innertube 302 and provide a more positive seal. Usually, since the blood willbe perfused at lower pressures than might be used for drug delivery, useof the balloon 316 for isolation will often not be necessary. Theperfusion conduit 300 can thus provided reduced flow resistance for theblood or other oxygenated medium being returned to the patient throughthe conduit. Additionally, the ability to slide the outer tube 304relative to the inner tube 302 helps the tubes be properly positionedrelative to each other depending on the circumstances of the patientbeing treated.

[0087] Referring now to FIG. 12, a perfusion conduit 400 intended forpassive perfusion, i.e., without active pumping, is illustrated. Thecatheter 400 usually comprises a single extrusion having a proximalsection 402 with an enlarged diameter and a distal section 404 with areduced diameter. The proximal and distal diameters will generally be inthe ranges set forth above. Blood inlet ports 408 are provided on thecatheter near its proximal end while blood outflow ports 410 areprovided near the distal end. The relative positions of the inflow ports408 and outflow ports 410 allow the perfusion conduit 400 to beintroduced to a patient so that the inflow ports are proximal to theocclusion while the outflow ports 410 are distal to the occlusion. Theinflow ports 408 are usually relatively near to the distal end of theproximal section 402 having the enlarged diameter in order to decreasethe overall flow resistance between the inflow ports 408 and outflowports 410. Generally, however, the inflow ports 408 will be positionedso that they will lie proximally of the occlusion so that the occludingmaterial does not block blood flow into the inflow ports. In someinstances, they will be spaced proximally of the transition 412 fromlarge diameter to small diameter by a distance in the range from 1 cm to15 cm, usually from 2 cm to 10 cm, to assure proper placement in thevasculature. The inflow ports 408 are thus able to receive blood andpass the blood distally through the large diameter section with minimumpressure drop. A pressure drop through the narrow diameter section 404will be greater, in many instances the total pressure drop of theconduit 400 will be sufficiently low so that adequate blood perfusioncan be maintained to relieve patient ischemia. Optionally, the conduit400 could have a slideable structure, as shown in conduit 300 of FIG.11, but such structure will increase the flow resistance and will not bepreferred in all instances. The conduit 400 preferably has a ID of 0.5mm to 1.8 mm, more preferably 0.75 to 1.5 mm, between the inflow andoutflow ports.

[0088] Referring to FIGS. 13 and 14, another catheter 500 is shown whichhas a perfusion conduit 502. The catheter 500 has a rounded, atraumaticdistal end 504 which is preferably guided through the vasculature over aguidewire which is advanced ahead of the catheter 500. The perfusionconduit 502 may have any of the shapes and sizes discussed herein andpreferably has a cross-sectional size of 0.77 to 7.1 mm2, morepreferably 1.7 to 2.9 mm2 along a distal portion 506 of the catheter500. In order to maintain adequate flow rates at acceptable pressures,the cross-sectional size is preferably at least 1.7, more preferably atleast 3.0 and most preferably at least 4.2 mm2 along the distal portion506. The distal portion 506 extends for a length of at least 5, 10, 15,20 or 25 cm from distal end 507 or from the most proximal outlet 518.

[0089] The catheter 500 and conduit 502 are sized large enough toprovide sufficient blood flow rates while blood pressure is withinallowable limits to prevent hemolysis. Specifically, the conduit 502 issized so that the pressure of oxygenated blood in the catheter is 0-400mmHg, more preferably 20-350 mmHg, at blood flow rates of at least 30,80, 120 or 160 ml/min. Furthermore, the overall length of the catheter500 is preferably at least 120, 150 or 175 cm depending upon the accesssite and size of the patient.

[0090] The overall maximum outer dimension of the catheter 500 shaftalong the distal portion 506 is preferably no more than 1.6 mm, 2.3 mm,or 3.2 mm. The various diameters and dimensions given throughout theapplication are equally applicable to any other suitable embodimentsdescribed herein. For example, all catheter dimensions discussed aboveare suitable dimensions for catheter 500 and all dimensions for catheter500 are applicable to other catheters described herein. Althoughcatheter 500 may include additional open lumens, such as ballooninflation, vent or pressure lumens, the catheter 500 preferably includesonly the perfusion conduit 502 to minimize the overall size. Thecatheter 500 may also be a passive inflation catheter such as thepassive inflation catheter 400 of FIG. 12.

[0091] The catheter 500 may include proximal and distal pressure sensors510, 512 for measuring pressure on both sides of the obstruction. In apreferred embodiment, the catheter 500 has only one pressure sensor 512and only the perfusion conduit 502. Wires 514 extending through or alongshaft are coupled to a pressure monitor 516 which in turn is integralwith or coupled to the control unit 110 for controlling the pump 100 inany manner described herein. The distal pressure sensor 512 ispreferably positioned a distance A which is at least 0.5 cm morepreferably at least 1 cm, from the most proximal outlet 518 so thatpressure measurement is not distorted by flow forces from the fluidperfused through the outlets 518. A heater and/or cooler 517 is alsoprovided for heating or cooling the oxygenated medium. The control unit110 also receives input control parameters 112 with the parametersmeasured with suitable sensors along the fluid line.

[0092] The pressure is preferably maintained below normal arterialpressure for a period of time to protect the previously ischemic bedfrom reperfusion injury. The inventor believes that prematurely exposingthe ischemic bed to normal arterial pressure may cause reperfusioninjury and that maintaining low pressure for a period of time canminimize or eliminate reperfusion injury. Low pressure in the previouslyischemic bed can be maintained by pressure feedback control of the pump100 as mentioned above. Alternatively, low pressure can be maintainedwithout direct measurement and feedback by simply selecting lowperfusion flow rates.

[0093] A second catheter 520 is slidably coupled to the catheter 500 andis advanced into the vascular system with the catheter 500 guiding thesecond catheter 520 to the obstruction. The catheter 500 passes througha hemostasis valve 521 in the second catheter 520. The second catheter520 passes over the catheter 500 but may also have an interlockingrelationship with the catheter 500. The second catheter 520 may also becompletely independent from the catheter 500 since advancing the secondcatheter 520 quickly may not be necessary with catheter 500 perfusingand protecting the previously ischemic vascular bed.

[0094] The second catheter 520 has a lumen 522 defined by the annularspace between the catheters 500, 520. The lumen 522 may be used todeliver liquids, including any of the therapeutic agents describedherein such as a thrombolytic agent, from a liquid source 524. Thesecond catheter 520 may also be coupled to a vacuum source 526 to ventblood, therapeutic byproducts and emboli through lumen 522.

[0095] The second catheter 520 may also include an obstruction removaldevice 528 for removing the obstruction. The obstruction removal device528 may simply be the distal tip of the catheter 520 which is used tomechanically remove the obstruction. The obstruction removal device 528may also be any suitable non-mechanical device such as an ultrasoundtransducer, an RF electrode, or a laser. FIG. 13 shows the obstructionremoval device 528 as an ultrasound transducer coupled to a power source531 (FIG. 14) with wires 534. The wires 534 may float within lumen 522or may be embedded in the wall of the catheter 520. If the obstructionremoval device is an RF electrode, a suitable second electrode (notshown) is placed in contact with the patient's body for monopolar RF oron either catheter 500, 520 for bipolar RF. An electrically conductivefluid, such as saline, may be passed through the lumen 522 from theliquid source 524 during activation of the RF electrode for enhancedconduction. Thus, the second catheter 520 is used to remove theobstruction by mechanical disruption, delivery of obstruction removingliquids through the lumen 522 or use of any of the other suitabledevices mentioned above.

[0096] Referring to FIG. 15, another perfusion catheter 600 is shownwhich has a perfusion conduit 602. The catheter 600 also has anexpandable member 604 which is preferably an inflatable balloon 606 butmay also be a mechanically actuated device. The expandable member 604prevents the previously ischemic bed from being exposed to full arterialpressure if the obstruction is cleared prematurely before the perfusiontherapy is completed. The balloon 606 may also be used to prevent partsof the obstruction or other emboli from flowing downstream beforetherapeutic agents or other obstruction removing methods are used todissolve, destroy, displace or otherwise remove the obstruction.

[0097] The balloon 606 has an inflation hole 608 leading to theperfusion conduit 602 so that perfusion of fluid through the conduit 602inflates the balloon 606. An advantage of using the perfusion conduit602 to inflate the balloon 606 is that a separate inflation lumen is notrequired which minimizes the size of the catheter 600. Referring to FIG.16, the perfusion catheter 600 may also include a separate inflationlumen 610 for inflating the balloon 606 so that the balloon 606 may beselectively inflated independent of perfusion. The balloon 606 may alsobe used for flow-directed placement of the catheter 600.

[0098] Referring to FIG. 17, a stent delivery catheter 700 is passedover the perfusion catheter 500, which may be any of the perfusioncatheters described herein, and a balloon 702 is used to expand a stent704 and open the artery. Referring to FIG. 18, a balloon catheter 706having a balloon 708 is advanced over the perfusion catheter 500. Theballoon 708 is expanded in the obstruction to displace the obstructionand open the artery. An advantage of the present system is that theperfusion catheter 500 perfuses and protects of the previously ischemicbed while the stent 704 or balloon 708 is positioned and deployed.

[0099] Referring to FIG. 19, another system 710 for treating thecerebral vasculature is shown. The system 710 includes the catheter 500which may be any of the catheters 10, 400, 600 described above or anyother suitable alternative. A catheter 712 passes through the catheter500 and is used to remove or displace the obstruction in the cerebralvasculature. As will be described in specific embodiments below, thecatheter 712 may be a balloon catheter 714 (FIGS. 20 and 21), a stentcatheter 716 (FIG. 22) or a perfusion catheter 718 (FIG. 23). Thecatheter 712 may, of course, use any other suitable method for removingthe obstruction including a laser, microwave, ultrasound, RF or amechanical device.

[0100] The system 710, and in particular the catheter 500, may also beused in any manner described above. For example, the catheter 500 may beused to infuse oxygenated medium to treat an ischemic region prior tointroduction of catheter 712. After infusion of the oxygenated mediumfor a period of time, the catheter 712 is used as described below. Thecatheter 500 preferably has the dimensions and characteristics of anysuitable catheter described herein. In particular, the lumen 502preferably has the necessary dimensions to provide for adequate infusionwhile being small enough to provide a flexible catheter which can passinto distal regions of the cerebral vasculature. The distal portion ispreferably at least 5, 10 15 or 20 cm in length. The lumen along thedistal portion has a cross-sectional area of 0.45 to 2.3, morepreferably 0.62 to 1.8, and most preferably 0.62 to 1.7 mm2. When thecross-sectional shape of the lumen is circular, the diameter of thelumen 502 is preferably 0.76-1.52 mm, more preferably 0.89-1.40 mm andmost preferably 0.89-1.27 mm along the distal portion. The maximumcross-sectional dimension along the distal portion (which is simply theouter diameter for a circular cross-section) is preferably no more than0.41 mm, 0.31 mm or 0.20 mm larger than the diameter of the lumen 502.Thus, the maximum cross-sectional dimension is preferably no more than1.2, 1.1 or 1.0 mm when the diameter of the lumen 502 is 0.76 mm.

[0101] The catheter 500 also preferably has a proximal portion whichextends for a length of at least 75 or 100 cm. The lumen 502 has across-sectional area of 2.0-7.6, more preferably 2.8-5.6 mm2, and mostpreferably about 3.2-5.1 mm2 along the proximal portion. When the lumen502 has a circular cross-sectional shape, the lumen 502 has a diameterof 1.52-2.92 mm, more preferably 01.09-2.67 mm, and most preferably1.89-2.54 mm. The maximum cross-sectional dimension along the proximalportion is preferably no more than 0.41, 0.31 or 0.20 mm larger than thediameter of the lumen 502. The catheter 500 may also have anintermediate section which has a length of 20-40 and preferably about 30cm. The intermediate section has a cross-sectional size between the sizealong the proximal and distal sections. In a preferred embodiment, theintermediate section has a constant taper between the proximal anddistal portions.

[0102] The catheter 500 has a hemostasis valve 713 which receives thecatheter 712. The introducer sheath 60 may also be used for introducingthe catheter and for withdrawing and directing blood and other fluidsfrom a fluid system 715 which is the system of FIGS. 7 or 14 describedabove.

[0103] An advantage of the catheter 500 is that the catheter 500 can beused to guide the balloon catheter 714, or any other catheter, to distalportions of the cerebral vasculature. Specifically, the catheter 500 isflexible enough to reach the middle cerebral artery M1 and M2 segments,anterior cerebral artery A1 and A2 segments, and basilar artery andpreferably to distal regions which are accessible depending upon thesize of the patient's vasculature. These regions are typically accessedby advancing the catheter over a guidewire rather than through anothercatheter. An advantage of using the catheter 500 rather than atraditional guidewire is that the catheter 500 protects the vasculatureas the catheter 500 is advanced. Another advantage is that the catheter500 may be used to infuse fluids, such as the oxygenated medium andtherapeutic agents prior to, during and after introduction of theobstruction removal catheter 712.

[0104] Referring to FIGS. 19 and. 20, the balloon catheter 714 has aballoon 718 which displaces the obstruction. An inflation lumen 720 iscoupled to a source of inflation fluid 722 (FIG. 19) for inflating theballoon 718. The catheter 714 may have more lumens, however, thecatheter 714 has only the inflation lumen 720 to minimize the size ofthe balloon catheter 714. Since the catheter 714 does not track over aconventional guidewire, the catheter 714 also does not have a guidewirelumen or other structure to track over a guidewire which further reducesthe size of the balloon catheter 714. The balloon catheter 714 alsopreferably has no distal opening so that the catheter 714 has a smooth,atraumatic tip which can be advanced through the obstruction ifnecessary. Thus, the balloon catheter 714 of the present inventionprovides advantages over conventional balloon catheters which track overguidewires.

[0105] The balloon catheter 714 is preferably sized and configured toprovide a space 723 between the catheters 714, 500 so that the lumen 502of catheter 500 may be used while the balloon catheter 714 is positionedtherein. The balloon catheter 714 may generally have the tapered shapewithin the range of shapes of the catheters 500 so that the ballooncatheter 714 essentially conforms to the shape of the lumen of thecatheter 500. Such a configuration facilitates advancement of theballoon catheter 714 through the catheter 500. The distal portion of thecatheter has a cross-sectional area of no more than 1.5 mm2 morepreferably no more than 1.0 mm2 over a distal portion 724 of thecatheter 714. The distal portion 724 preferably extends at least 5 cmand more preferably at least 10 cm from a distal end 726. The maximumouter dimension of the catheter 714 over the distal portion 724 may alsobe no more than 1.2 mm, 0.8 mm, 0.75 mm and most preferably no more than0.65 mm in diameter.

[0106] In another preferred method of the present invention, thecatheter 500 is advanced through the obstruction to infuse oxygenatedmedium into the ischemic bed as described above. When the ischemic bedhas been adequately perfused at the desired rates and pressures, thecatheter 500 may be withdrawn through the obstruction. During withdrawalof the catheter, the lumen 502 may be coupled to the vacuum source 526to capture emboli (FIG. 19). The balloon 718 may be positioned to liewithin the obstruction as the catheter 500 is withdrawn, it may beadvanced by itself through the obstruction after withdrawal of thecatheter, or may be pulled back to lie within the obstruction byadvancing the balloon beyond the obstruction within the catheter 500before withdrawing the catheter 500. Once the balloon 718 is positionedwithin the obstruction, the balloon 718 is inflated to displace theobstruction as shown in FIG. 20. The lumen 502 may also be used to ventblood and thereby suction emboli while inflating the balloon 718.Although the catheter 714 preferably has only the inflation lumen 722,the catheter 714 may also have in infusion lumen 728 as shown in FIG.21. The infusion lumen 728 is coupled to the system of FIG. 7 or 14 toinfuse oxygenated medium and other fluids distal to the obstruction asdescribed above, but the catheter 714 is otherwise used in the samemanner as catheter 714.

[0107] Referring to FIG. 22, another system is shown which is similar tothe system of FIG. 19 except that the stent catheter 716 is used insteadof the balloon catheter 714. The stent catheter 716 is used insubstantially the same manner as the balloon catheter 714 in that astent 732 displaces the obstruction. The stent 732 is mounted to aballoon 734 having a lumen 736 coupled to the inflation source 722. Theinflation lumen 736 is preferably sized like the lumen 728 and thepreferred dimensions of the stent catheter 716 are the same as describedabove for the balloon catheter 714. The stent catheter 716 offers thesame advantages as the balloon catheter 714 in that the stent catheter716 does not require a guidewire lumen or other structure to track overa conventional guidewire. The stent 732 may be a suitable conventionalstent 732 mounted to the catheter 716 of the present invention. Thestent catheter 716 may also have a perfusion lumen and outlet 719, whichmay be a number of outlets or sideholes, for perfusing fluids asdescribed above.

[0108] Referring to FIG. 23, the catheter 712 may also be the perfusioncatheter 718 which passes through the catheter 500. The perfusioncatheter 718 has a lumen 738 coupled to a source of solution 740 whichis used to remove or dissolve the obstruction (FIG. 19). The perfusioncatheter 718 is advanced through the catheter 500 so that openings 740are positioned in or near the obstruction. The openings 740 may be atthe distal end or spaced from the distal end. The catheter 500 is thenwithdrawn through the obstruction while venting through the lumen 738with the vacuum source 526 to remove emboli. After the catheter 500 hasbeen withdrawn, the solution is delivered through the perfusion catheter718 and the dissolved obstruction can be withdrawn through the lumen 502in the catheter 500 using the vacuum source 526. The catheter 500 andperfusion catheter 718 are both coupled to the system of FIGS. 7 or 14for periodic infusion of the oxygenated medium as necessary. The lumen738 preferably has a cross-sectional area of no more than 1.54 mm2 andmore preferably no more than 0.3 mm2, and most preferably no more than0.19 mm2 along the distal portion of at least 5 cm. The maximum outerdimension of the catheter along the distal portion is preferably no morethan 1.4 mm and more preferably no more than 0.95 mm and most preferablyno more than 0.50 mm so that the lumen of the catheter 500 may still beused to suction the dissolved obstruction with the perfusion catheter718 contained therein.

[0109] Although it is preferred to pass the catheters 714, 716, 718directly through the catheter 500 thereby obviating the need to trackover a guidewire, the catheters 714, 716, 718 may also be advanced overa guidewire which is advanced through the vasculature within the lumen502 of catheter 500. Conventional guidewires are typically 0.014 inch to0.018 inch in diameter and constructed to be flexible enough to reachthe distal regions of the cerebral vasculature described above. Afterthe guidewire has reached the desired location, a catheter can beadvanced over the guidewire. At this point in the procedure, theguidewire must be rigid, rather than flexible, so that the cathetertracks over the guidewire without displacing the guidewire itself.

[0110] The devices and methods of the present invention permit the useof relatively large guidewires for advancement of catheters through thecerebral vasculature. This system does not require the use of smaller,more flexible guidewires since the guidewire is advanced through thecatheter 500 rather than independently. The system promotes significantstability beyond that provided by conventional guidewires. The guidewireand corresponding guidewire lumen size of the catheter 712 arepreferably larger than 0.018 inch, at least 0.028 inch, or at least0.035 inch. The catheter 500 may then be removed and the catheter 712advanced over the large stable guidewire. The catheter 500, or anotherperfusion catheter described herein, and the catheter 712 and/orguidewire may be packaged together in a kit for practicing the method asshown in FIG. 9.

[0111] Referring to FIG. 24, yet another system 740 for treating anobstruction in the cerebral vasculature is shown. The system 740includes a first catheter 742 which passes through a second catheter743. The first catheter 742 is coupled to the system of FIGS. 7 or 14for infusion of fluids in the manner described above. The secondcatheter 743 is coupled to a source of inflation fluid 744 for inflatinga balloon 745. The system 740 is similar to the systems described abovein that the first catheter 742 infuses the oxygenated medium while theballoon 745 displaces the obstruction. The first and second catheters742, 743 are both tapered with the first catheter 742 positioned withinthe second catheter 743 with a close tolerance fit to reduce the overallsize of the system. The catheters 742, 743 preferably have dimensions ofthe tapered catheters described above. Referring to FIGS. 24 and 25, thefirst catheter 742 may have a coiled tip 748 similar to a guidewire ormay have a tubular shape similar to a catheter. Referring to FIGS. 26and 27, the first catheter 742 has a lumen 749 which is coupled to thesystem of FIGS. 7 or 14. An inflation lumen 744 may have a smallercross-sectional size (FIG. 26) in a deflated position state relative toan inflated state (FIG. 27).

[0112] Another preferred method of the invention is now described withreference to FIG. 24. The second catheter 743 is advanced over aconventional guidewire (not shown) to a position within or near theobstruction. The guidewire is then removed and the first catheter 742 isintroduced through the second catheter 743. The first catheter 742 isthen advanced through the obstruction together with the second catheter743 or by itself. Oxygenated medium is then delivered in the mannerdescribed above. After infusing the oxygenated medium for the desiredtime at the desired rates and pressures, the balloon 745 on the secondcatheter 743 is inflated to displace the obstruction. The balloon 745may also be used to isolate the ischemic region from normal arterialflow.

[0113] Referring to FIGS. 28-30, an alternative second catheter 743A isshown which may be used in the same manner as second catheter 743 ofFIGS. 24-27. The second catheter 743A has an expandable sidewall 760which is folded or wrapped in a collapsed position and advanced over aguidewire 761 as shown in FIG. 29. The sidewall 760 provides a smallprofile when advanced through the vasculature and a large capacity foruse in delivering fluids or other catheters as described above. Thesidewall 760 preferably reduces the maximum outer dimension of thecatheter along a portion by at least 25% while retaining the overalldimensions of the catheter 500 when in the expanded configuration. Aninflation lumen 752 is coupled to the balloon 745 for inflating theballoon 745. The sidewall 760 may be made of any suitable material andis preferably a thermoplastic material having a wall thickness of nomore than 0.38 mm and preferably no more than 0.25 mm. The sidewall 760may be used with any of the other catheters described herein and isparticularly advantageous for the catheters 10, 400, 500, 600. Thesidewall 760 may take other forms without departing from the scope ofthe invention.

[0114] The second catheter 743A is advanced over the guidewire 761 withthe sidewall 760 in the collapsed condition. When the balloon 745 ispositioned proximate to the obstruction, the first catheter 742 isadvanced through the catheter 743A. The sidewall 760 is expanded by thefirst catheter 742 to the expanded position of FIG. 24. The sheath 760may also be expanded by an obturator or the like before introduction ofthe catheter 742. The first and second catheters 742, 743A may be thenused in any manner described above.

[0115] The devices 10, 400, 500, 600 described above may be manufacturedin any suitable conventional manner. Although conventional methods maybe used to manufacture the devices described above, a preferred methodof constructing the devices is now described below in connection withFIGS. 31-34. Referring to FIG. 31, an exploded view of a preferredconstruction of an intravascular device 802 is shown. The intravasculardevice 802 may be used in any manner described above and the discussionabove is incorporated here. For example, the device 802 may be used todeliver oxygenated media to a previously ischemic region or to deliverother interventional devices. The intravascular device 802 may also beused in other parts of the vascular system without departing from thescope of the invention.

[0116] The basic construction and method of constructing the device 802are now described in general terms and more specific details are givenbelow. A liner 804 is mounted to a mandrel 806. The liner 804 forms theinner lining of a lumen 807 extending through the device 802. Areinforcing layer 808 is positioned over the liner 804. The reinforcinglayer 808 is preferably wound or braided onto the liner 804 and may be acoil 810 or a woven or braided structure 812. A jacket 814 is thenpositioned over the reinforcing layer 808. A shrink tube 815 is thenpositioned over the jacket 814 and heated to melt and fuse the layers804, 814 together to form an integrated structure as shown in FIG. 33.Although the preferred construction includes only the liner 804,reinforcing layer 808 and jacket 814, the device 802 may include otherlayers and may have coatings, such as a heparin-type or hydrophiliccoating, which cover the inner and/or outer surfaces without departingfrom the scope of the invention.

[0117] The mandrel 806 generally defines the interior geometry of thelumen 807 and preferred dimensions of the lumens described above areapplicable here. The mandrel 806 has a proximal portion 816, anintermediate portion 818, and a distal portion 820. The distal portion820 preferably has a constant inner diameter of 0.030-0.050 inch, morepreferably 0.040-0.050 inch and most preferably about 0.046 inch. Thedistal portion preferably extends at least 10 cm and more preferably atleast 15 cm from a distal end 822. The intermediate portion 818 tapersup from 0.046 to at least 0.070 inch, more preferably at least 0.080inch and most preferably about 0.085 inch and extends 30 cm between afirst transition 824 and a second transition 826. The proximal portion816 preferably has a constant inner diameter of 0.070 to 0.100 inch,more preferably 0.080 to 0.090 inch and preferably about 0.085 inch fora length of at least 80 cm and more preferably about 105 cm to aproximal end 827. Although the lumen 807 has the dimensions describedabove for the mandrel 806, the lumen 806 may also be within the lumensize ranges given above in connection with any of the embodimentsdescribed above.

[0118] The liner 804 has a distal portion 828 which is made of expandedPTFE and a proximal portion 830 which is made of etched PTFE. Anadvantage of using expanded PTFE is that the distal portion 828 has aflexibility which is greater than with etched PTFE. Another advantage ofthe liner 804 is that the two different PTFE materials provide differingcolumn strength and tip deflection for the proximal and distal sections830, 828. The distal portion 828 has the expanded PTFE to provideflexibility to navigate small and tortuous vessels. The stiffer proximalportion 830 has the etched PTFE liner which provides pushability andcolumn strength for advancement of the device 802 through the vascularsystem. The distal portion 828 preferably extends 15-25 cm and morepreferably about 21 cm from the distal end 822 but may extend the lengthof the device. The proximal portion 830 preferably overlaps the distalportion 828 for about 0.3 cm with the distal portion 828 positionedinside the proximal portion 830 to reduce pressure drop at thetransition of the proximal and distal portions 828, 830. A suitablematerial for the distal portion 828 of the liner 804 is expanded PTFEhaving a wall thickness of 0.002 inch and a diameter of 0.037 inch. Theexpanded PTFE is stretched onto the mandrel which has a diameter of0.046 inch. A suitable material for the proximal portion 830 of theliner 804 is etched PTFE having a wall thickness of 0.002 inch and adiameter of 0.093 which is shrunk onto the mandrel which has a diameterof 0.046-0.085 inch. The etched PTFE is shrunk onto the mandrel withheat and tension. The expanded PTFE preferably has an internodal spacingof 10-120 microns, more preferably 10-60 microns and most preferablyabout 20-30 microns. The proximal and distal portions 830, 828 may, ofcourse, both be made of the same material, such as etched PTFE orexpanded PTFE, without departing from the scope of other aspects of thepresent invention.

[0119] The reinforcing layer 808 has a number of sections, preferably atleast four and more preferably at least five sections, to vary theflexibility along the device 802. The high variability permits use ofthe device 802 without a guiding catheter as described above although aguide catheter may be used without departing from the scope of theinvention. The reinforcing layer 808 has a first section 832, a secondsection 834, a third section 836, a fourth section 838 and a fifthsection 840. The first section 832 is a coil reinforcing element 842extending along the distal portion 820 of the mandrel 806 just beyondthe transition 824 to the tapered, intermediate portion 818, preferablyabout 19 cm from the distal end 822 and 4 cm beyond the transition 824.The coil 842 is preferably 0.003 inch diameter stainless steel wirewound to have a centerline spacing of about 0.012 inch. The second,third, fourth and fifth sections 834, 836, 838, 840 are preferablybraided 0.003 inch diameter stainless steel wire. The second, third,fourth and fifth sections 834, 836, 838, 840 are shown separated forclarity but are preferably continuously wound with the pic beingautomatically varied during winding. The second section 834 overlaps thefirst section for about 1 cm and begins about 18 cm from the distal end.The second section 834 has 70 pics, the third section 836 has 60 pics,the fourth section 838 has 50 pics and the fifth section 840 has 30pics. The second section 834 extends 7 cm, the third section 836 extends7 cm, the fourth section 838 extends 7 cm through the transition 826,and the fifth section extends to the proximal end 827. Although thereinforcing layer has the specific characteristics described above, thesections may vary as follows. The second section 834 preferably has apic which is at least 15 more, and more preferably at least 20 more,than the fourth section 838. The second section 834 is preferablyseparated from the fourth section 838 by no more than 15 cm andpreferably no more than 10 cm. The first section preferably has a picwhich is at least 30 pics more than the fifth section 840 with the firstsection separated from the fifth section by no more than 20 cm and morepreferably no more than 15 cm. Although the reinforcing layer 808 hasthe preferred characteristics described above, the reinforcing layer 808may be any suitable structure and may be entirely coil, braid, or weave.The reinforcing layer 808 may also be made of any suitable material suchas shape memory alloy or polymer.

[0120] The jacket 814 preferably includes a number of sections,preferably at least four, more preferably at least five and mostpreferably at least six sections, which also enhance variation inflexibility. The high variation in flexibility provides good flexibilityat the distal portion while providing column strength at the proximalportion to advance the device 802 and prevent kinking. The highvariability in the jacket 814 also provides a smooth transition instiffness between the distal and proximal sections. The jacket 814 hasfirst, second, third, fourth, fifth and sixth liner sections 846, 848,850, 852, 854, 856 which are mounted next to one another on the mandrel806. The flexural modulus of the jacket preferably increases at least25, more preferably at least 40 times, and most preferably about 55times from the first section 846 to the sixth section 856. Specifically,the jacket flexural modulus increases from 2000 psi at the first section846 to 110,000 at the sixth section 856. The flexural modulus of thejacket 814 also increases at least 10 times, more preferably at least 15times and most preferably about 17.5 times over a 10 cm distance fromthe second section 848 to the fifth section 854.

[0121] The jacket sections also preferably increases in durometertowards the proximal end. The durometers of the sections are as follows;the first section 846 is 25 D, the second section 848 is 35 D, the thirdsection 850 is 40 D, the fourth section 852 is 55 D, the fifth section854 is 63 D, and the sixth section 856 is 72 D. The sections extend forthe following lengths, the first section 846 extends 7 cm from thedistal end 822, the second section 848 extends 3 cm, the third section850 extends 3 cm, the fourth section 852 extends 3 cm through thetransition 824 to the intermediate portion 818, the fifth section 854extends 9 cm along the intermediate portion 818, and the sixth section856 extends 125 cm. The first, second, third and fourth sections 846,848, 850, 852 have an inner diameter of 0.080 inch. The fifth section854, which extends through the tapered, intermediate section 818, has adiameter of about 0.095 inch and the sixth section 856 has a diameter of0.105 inch. All jackets sections are preferably made of pellethane,polyurethane or the like. The dimensions may, of course, be modifiedwithout departing from the scope of the invention.

[0122] As mentioned above, the liner 804, reinforcing elements 808 andjacket 814 are mounted on the mandrel 806. Other layers may bepositioned over the jacket 814 but in the preferred embodiment thejacket 814 forms the outer layer of the device 802. The shrink tube 815is positioned over the jacket 814 as shown in FIG. 32 and the entirestructure is heated to form the integrated structure 860 of FIG. 33. Theresulting wall thickness of the device 802 is about 0.005 inch,preferably 0.004 to 0.007 inch, along the distal portion 820 of theliner 804. The wall thickness of the proximal portion 816 tapers up from0.005 inch to 0.015 inch from the end of the first section of thereinforcing layer to the proximal end. Although the preferred embodimentprovides specific jacket sections and reinforcement construction, theflexibility of the device may be provided by other combinations ofjacket 814 and reinforcing layer without departing from the scope of theinvention.

[0123] The gradual change in stiffness also provides an advantage whenadvancing the catheter through small, tortuous vessels. Conventionalmicrocatheters must be advanced over a guidewire since themicrocatheters do not have sufficient column strength to be advancedwithout the aid of a guidewire. The catheter of the present inventioncan be advanced through the vasculature without the aid of a guidewirealthough a guidewire may be used when needed. The change in stiffnesshelps to resists buckling at the proximal portion while retainingsufficient flexibility at the distal portion to navigate small andtortuous vessels. Conventional microcatheters have low column strengthat the distal portion which requires the micrcatheters to be advancedover a guidewire. The guidewire generally has an outer diameter within0.005 inch of the inner diameter of the lumen so that the guidewiresupports the distal portion to prevent kinking. The distal portion ofthe present catheter has sufficient column strength to be advancedwithout a guidewire.

[0124] In a specific application of the present invention, the catheteris advanced to the common carotid artery over a conventional guidewiresuch as an 0.035 inch diameter guidewire. The distal portion is thenadvanced without the aid of a guidewire into intracranial vessels havinga size of 4-5 mm and even 3 mm in diameter. Stated another way, thecatheter of the present invention may be used to access vessels such asthe middle or anterior cerebral arteries and the vertebral, basilar andposterior cerebral arteries when accessing the cerebral vasculature.

[0125] The catheter of the present invention also has a high change inflexibility from a proximal portion to a distal portion. Specifically,the proximal section is at least 20, 40, 60 or even 75 times stifferthan the distal portion of the catheter. The distal portion preferablyextends at least 5, more preferably at least 10, and more preferably atleast 15 cm from the distal end while the proximal portion extends towithin 40, 35 and most preferably to within 30 cm from the distal end orcloser. The high change in stiffness permits the proximal portion to berigid enough to prevent buckling and kinking while the distal portion isflexible to pass through tortuous vessels.

[0126] Referring to FIG. 34, the distal end 822 of the device is shownwith the distal portion 828 of the liner 804 extending beyond thereinforcing layer 808 and the jacket 814 after heating to form theintegrated structure. The end of the liner 804 is everted to form asoft, atraumatic distal end. The end of the liner 804 is everted for alength of at least 0.5 mm, more preferably 1-2 mm, and preferably 2 mmto form the soft tip. Use of the expanded PTFE material for the distalportion 828 provides a soft tip which helps to navigate the devicethrough small and tortuous vessels. The proximal end is then attached tothe necessary connectors and hemostasis valves so that the device 802forms all or part of the intravascular device such as the devices 10,400, 500, 600 described above. The device 802 may, of course, be usedfor other procedures and in other parts of the body.

[0127] Referring to FIGS. 31, 35 and 36, another device 802A is shownwhich has the lumen 807 and an additional lumen 860 wherein the same orsimilar reference numbers refer to the same or similar structure. FIG.35 shows a cross-sectional view along the distal portion and FIG. 36 isa cross-sectional view of the device 802A along the proximal portion.The device 802A is constructed in substantially the same manner as thedevice 802 and the discussion above is equally applicable here. Thelumen 860 is formed by a tube 862 which is essentially bonded to thedevice 802 in the manner described below. The lumen 860 preferably has across-sectional area of 0.050 to 0.620 mm2 and more preferably 0.200 to0.400 mm2.

[0128] The tube 862 is preferably a polyimide tube having an innerdiameter of 0.020-0.035 inch, preferably about 0.026 inch, with a wallthickness of 0.001 to 0.002 inch. Of course, any other suitable materialand size may be used. The tube 862 has a length of about 134 cm with anopening 864 positioned 5-26 cm, more preferably 10-26 cm, and mostpreferably about 18 cm from the distal end of the device 802A. Theopening 864 may also be closer to the distal end without departing fromthe scope of the invention. The opening 864 is preferably positionedalong the tapered portion of the device 802A but may also be at theconstant diameter distal portion. The opening 864 is shown formed in thetube 862 in FIG. 31 for clarity, however, the opening 864 is preferablyformed after forming the integrated structure of FIGS. 35 and 36 asdescribed below.

[0129] The tube 862 is preferably rolled through a die to create anoblong cross-sectional shape. The tube 862 is then positioned over thejacket 814 and is covered by the shrink tube as described above. Thejacket 814 is positioned over the reinforcing layer 808 and liner 804 inthe manner described above. The tube 862 is preferably coated with apolymer, such as polyurethane having a thickness of 0.002-0.003 inch,which fuses with the jacket 814 when melted. The tube 862 may melt andfuse with the jacket 814 or may be designed to remain solid duringheating as shown in FIGS. 35 and 36. The end of the tube 862 is crimpedto close the distal end and the opening 864 is formed after forming theintegrated structure of FIG. 35. A teflon-coated mandrel may bepositioned in the tube 862 to hold the tube 862 open during heating andmelting.

[0130] The device 802A may be used in any manner described above and thediscussion above is equally applicable here. Furthermore, the device860A may have the features of the other multi-lumen devices describedherein and the discussion of the various dimensions and preferred usesdescribed herein are also applicable here. For example, the device 802Amay be used to deliver an oxygenated medium to a previously ischemicregion in the manner described above. The lumen 860 may be used todeliver thrombolytic, anticoagulant and/or anti-restenotic agents. Thelumen 860 may also be used to deliver contrast or to measure pressure.

[0131] While the above is a complete description of the preferredembodiments, various alternatives, modifications, and equivalents may beused. The terms first liner, second liner . . . or first portion, secondportion are used for ease of reference in the drawings and figures,however, these terms may refer to other sections or portions withoutdeparting from the scope of the invention. Thus, when the claims recitethat a first liner section has a preferred durometer change with respectto a third liner section, the first and third sections in the claims mayactually refer to a second and fourth liner sections or to fourth andsixth liner sections without departing from the scope of the claims.Therefore, the above description should not be taken as limiting thescope of the invention which is defined by the appended claims.

What is claimed is:
 1. A method of forming an intravascular device,comprising the steps of: mounting an expanded PTFE liner over a firstmandrel portion; winding a reinforcing layer over the expanded PTFEliner after the mounting step; and applying a first jacket over thereinforcing layer and expanded PTFE liner after the winding and mountingsteps.
 2. The method of claim 1, further comprising the steps of:covering the jacket, reinforcing layer and expanded PTFE liner with ashrink tube; fusing the coating layer to the expanded PTFE liner to forman integrated structure; and removing the shrink tube after the fusingstep.
 3. The method of claim 1, wherein: the applying step is carriedout by positioning a tube of material over the reinforcing layer.
 4. Themethod of claim 1, further comprising the steps of: positioning anetched PTFE liner over a second mandrel portion; and the winding step iscarried out with the reinforcing layer being wound over the etched PTFEliner; and the applying step is carried out with the jacket layer beingpositioned over the reinforcing layer and the etched PTFE liner afterthe winding step.
 5. The method of claim 4, wherein: the applying stepsare carried out with the jacket layer having a first jacket section anda second jacket section, the first jacket section being positioned overthe expanded PTFE liner and the second jacket section being positionedover the etched PTFE liner, the first jacket section having a durometerwhich is at least 30 D less than the second jacket section.
 6. Themethod of claim 5, wherein: the applying steps are carried out with thefirst jacket section having a durometer which is at least 40 D less thanthe second jacket section.
 7. The method of claim 1, wherein: thepositioning steps are carried out with the expanded PTFE liner having aporosity of 8-10 microns.
 8. The method of claim 4, wherein: the firstmandrel portion and second mandrel portion are part of the same mandrel.9. The method of claim 1, further comprising the step of: inverting anend of the expanded PTFE liner at a distal end.
 10. The method of claim9, wherein: the inverting step is carried out to form an invertedportion of the expanded PTFE liner which extends longitudinally at least0.5 mm from a distal end of the reinforcing element.
 11. Anintravascular device, comprising: a liner layer having a first linersection, the first liner section being made of expanded PTFE; areinforcing layer wound over the liner layer; and a jacket positionedover the reinforcing layer and fused with the liner layer.
 12. Thedevice of claim 11, wherein: the liner has a second liner section, thesecond liner section being made of a material which is stiffer than theexpanded PTFE of the first liner section.
 13. The device of claim 12,wherein: the second liner section is made of etched PTFE.
 14. The deviceof claim 13, wherein: the expanded PTFE has a porosity of 8-10 microns.15. An intravascular device for accessing small diameter, tortuousvessels, comprising: a shaft having a stiffness transition zone, thestiffness transition zone extending 20 to 30 cm from the distal end, thestiffness of the device increasing no more than 600% over any 4 cmportion of the stiffness transition zone; and at least one lumenextending through the shaft.
 16. The device of claim 15, wherein: thestiffness of the device increases no more than 500% over any 4 cmportion of the stiffness transition zone.
 17. The device of claim 15wherein: the shaft has a liner portion which lines the at least onelumen, the liner portion comprising expanded PTFE.
 18. The device ofclaim 17, wherein: the liner portion also comprises etched PTFE.
 19. Thedevice of claim 15, wherein: the lumen has a cross-sectional areathrough the distal portion of 0.77 to 7.1 mm2.
 20. The device of claim15, wherein: the lumen has a cross-sectional area through the proximalportion of 1.7 to 2.9 mm2.
 21. The device of claim 15, wherein: thestiffness transition zone coincides with at least a portion of anintermediate, tapered region of the lumen.
 22. The device of claim 21,wherein: the proximal portion has a constant cross-sectional area; thedistal portion has a constant cross-sectional area; and the intermediatesection is tapered and extends between the proximal and distal portions.23. The device of claim 15, wherein: the distal portion has an expandedPTFE liner; and the proximal portion has an etched PTFE liner.
 24. Thedevice of claim 15, wherein: the distal portion has a wall thickness of0.004 to 0.007 inch.
 25. The device of claim 15, wherein: the proximalportion has a wall thickness of between 0.003 to 0.013 inch.
 26. Thedevice of claim 15, wherein: the distal portion is formed by a liner, atleast one reinforcing element, and a jacket over the liner and thereinforcing element, the jacket having a first section, a secondsection, and a third section, the first section having a durometer whichis at least 13 D less than the third section, the second section havinga durometer between the first and third sections, the first and thirdsections being separated by a longitudinal distance of 10 cm or less.27. The device of claim 26, wherein: the first and third sections areseparated by a longitudinal distance of 8 cm or less.
 28. The device ofclaim 26, wherein: the shaft has a fourth section which is positionednext to the third section, the first section having a durometer which isat least 25 D less than the fourth section, the first section beingseparated from the fourth section by a longitudinal distance of 15 cm orless.
 29. The device of claim 28, wherein: the positioning step iscarried out with the first section being separated from the fourthsection by a longitudinal distance of 10 cm or less.
 30. A method ofadvancing an intravascular device into small diameter, tortuous vessels,comprising the steps of: providing a catheter having a lumen extendingtherethrough, the lumen having a cross-sectional size of 0.77 to 7.1mm2; introducing the catheter into the patient vascular system; andadvancing the catheter through vessels having a diameter of 3 mm to 5 mmwithout advancing the catheter over a guidewire.
 31. The method of claim30, wherein: the advancing step being carried out with the catheterhaving an open end at the distal end.
 32. The method of claim 30,wherein: the providing step is carried out with the lumen having across-sectional size of 1.7 to 2.9 mm2.
 33. The method of claim 30,wherein: the providing step is carried out with the catheter having aconstant diameter proximal portion, a tapered intermediate portion, anda constant diameter distal portion.
 34. The method of claim 30, wherein:the providing step is carried out with the catheter having a stiffnesstransition zone from 20-40 cm from the distal end, the stiffness of thecatheter increasing by no more than 600% over any 4 cm length throughthe stiffness transition zone.
 35. A method of forming an intravasculardevice, comprising the steps of: providing a mandrel; mounting a firstliner on the mandrel; winding a reinforcing layer over the first liner;positioning a first jacket, a second jacket and a third jacket over thereinforcing layer, the second jacket being positioned between the firstand third jackets, the first jacket having a durometer which is at least13 D less than the third jacket, the second jacket having a durometerbetween the first and third jackets; and fusing at least the first,second and third jackets to the liner to encase the reinforcing layerbetween the first liner and the first, second and third jackets.
 36. Themethod of claim 35, wherein: the positioning step is carried out withthe first jacket having a durometer of at least 15 D less than the thirdjacket.
 37. The method of claim 35, wherein: the first and third jacketsare separated by a longitudinal distance of 10 cm or less.
 38. Themethod of claim 37, wherein: the first and third jackets are separatedby a longitudinal distance of 8 cm or less.
 39. The method of claim 38,wherein: the first and third jackets are separated by a longitudinaldistance of 5 cm or less.
 40. The method of claim 35, wherein: thepositioning step is carried out with a fourth jacket which is positionednext to the third jacket, the first jacket having a durometer which isat least 25 D less than the fourth jacket.
 41. The method of claim 40,wherein: the positioning step is carried out with the first jacket beingseparated from the fourth jacket by a longitudinal distance of 15 cm orless.
 42. The method of claim 40 wherein: the positioning step iscarried out with the first jacket being separated from the fourth jacketby a longitudinal distance of 10 cm or less.
 43. The method of claim 35,wherein: the positioning step is carried out with a fifth jacket whichis positioned next to the fourth jacket, the first jacket having adurometer which is at least 28 D less than the fourth jacket.
 44. Themethod of claim 43, wherein: the positioning step is carried out withthe first jacket being separated from the fifth jacket by a longitudinaldistance 20 cm or less.
 45. The method of claim 43 wherein: thepositioning step is carried out with the first jacket being separatedfrom the fifth jacket by a longitudinal distance of 15 cm or less. 46.The method of claim 35, wherein: the positioning step is carried outwith a sixth jacket which is positioned next to the fifth jacket, thefirst jacket having a durometer which is at least 40 D less than thesixth jacket.
 47. The method of claim 46, wherein: the positioning stepis carried out with the first jacket being separated from the sixthjacket by a longitudinal distance of 25 cm or less.
 48. The method ofclaim 46 wherein: the positioning step is carried out with the firstjacket being separated from the fifth jacket by a longitudinal distanceof 20 cm or less.
 49. An intravascular device, comprising: a shafthaving a lumen extending therethrough; a reinforcing layer embedded inthe shaft; and the shaft having a first jacket, a second jacket and athird jacket covering the at least one reinforcing element, the secondjacket being positioned between the first and third jackets, the firstjacket having a durometer which is at least 13 D less than the thirdjacket, the second jacket having a durometer between the first and thirdjackets.
 50. The device of claim 49, wherein: the first jacket has adurometer of at least 15 D less than the third jacket.
 51. The device ofclaim 49, wherein: the first and third jackets are separated by alongitudinal distance of 10 cm or less.
 52. The device of claim 49,wherein: the first and third jackets are separated by a longitudinaldistance of 8 cm or less.
 53. The device of claim 52, wherein: the firstand third jackets are separated by a longitudinal distance of 5 cm orless.
 54. The device of claim 49, wherein: the shaft has a fourth jacketwhich is positioned next to the third jacket, the first jacket having adurometer which is at least 25 D less than the fourth jacket.
 55. Thedevice of claim 54, wherein: the first jacket being separated from thefourth jacket by a longitudinal distance of 15 cm or less.
 56. Thedevice of claim 54 wherein: the first jacket is separated from thefourth jacket by a longitudinal distance of 10 cm or less.
 57. Thedevice of claim 49, wherein: the shaft has a fifth jacket which ispositioned next to the fourth jacket, the first jacket having adurometer which is at least 28 D less than the fourth jacket.
 58. Thedevice of claim 57, wherein: the first jacket is separated from thefifth jacket by a longitudinal distance 20 cm or less.
 59. The device ofclaim 57 wherein: the first jacket is separated from the fifth jacket bya longitudinal distance of 15 cm or less.
 60. The device of claim 49,wherein: the shaft has a sixth jacket which is positioned next to thefifth jacket, the first jacket having a durometer which is at least 40 Dless than the sixth jacket.
 61. The device of claim 60, wherein: thefirst jacket is separated from the sixth jacket by a longitudinaldistance of 25 cm or less.
 62. The device of claim 60 wherein: the firstjacket is separated from the sixth jacket by a longitudinal distance of20 cm or less.
 63. The device of claim 49, wherein: the reinforcinglayer has a braided portion, the braided portion having a first section,a second section and a third section, the first section has a pic whichis at least 15 more than the third section.
 64. The device of claim 63,wherein: the third section is separated from the first section by nomore than 15 cm.
 65. The device of claim 63, wherein: the third sectionis separated from the first section by no more than 10 cm.
 66. Thedevice of claim 63, wherein: the reinforcing layer has a fourth section,the first section has a pic which is at least 30 pics more than thefourth section, the first section being separated from the fourthsection by no more than 20 cm.
 67. The device of claim 66, wherein: thefirst section is separated by the fourth section by no more than 15 cm.68. An intravascular device for accessing small, tortuous vessels,comprising: a shaft having at least four sections of varying stiffness,the shaft becoming more stiff proximally; and a lumen extending throughthe shaft.
 69. The device of claim 68, wherein: the shaft is formed by aliner, a reinforcing layer, and a jacket, the reinforcing layer beingpositioned between the liner and jacket.
 70. The device of claim 69,wherein: the at least four sections of varying stiffness are provided byvarying the durometer of the jacket and a spacing between windings ofthe reinforcing layer.
 71. The device of claim 69, wherein: the shafthas at least five sections of varying stiffness.
 72. The device of claim69, wherein: the shaft has at least six sections of varying stiffness.73. A method of advancing a catheter through small, tortuous vessels,comprising the steps: providing a catheter having a proximal portion anda distal portion, the distal portion extending at least 10 cm from thedistal end and the proximal portion extending within 40 cm from thedistal end or closer, the proximal portion being at least 20 timesstiffer than the distal portion, the catheter having a lumen with thelumen along the distal portion having a diameter of 0.040 to 0.060 inch;introducing the catheter into a patient; and advancing the catheterthrough the patient's vasculature to a desired site.
 74. The method ofclaim 73, wherein: the providing step is carried out with the proximalportion being at least 40 times stiffer than the distal portion.
 75. Themethod of claim 73, wherein: the providing step is carried out with theproximal portion being at least 60 times stiffer than the distalportion.
 76. The method of claim 73, wherein: the providing step iscarried out with the lumen along the proximal portion having an innerdiameter of 0.070 a to0.010 inch.
 77. The method of claim 72, wherein:the advancing step is carried out with the distal portion being advancedthrough to the desired site without the aid of a guidewire.
 78. A methodof advancing a catheter into small diameter vessels, comprising thesteps of: providing a catheter having a distal portion and a proximalportion, the catheter also having a lumen extending through the proximaland distal portions, the lumen along the distal portion having an innerdiameter of 0.040 to 0.050 inch; introducing the catheter into apatient's vascular system; and advancing the catheter through vesselshaving a size of less than 5 mm without the aid of a guidewire.
 79. Themethod of claim 77, wherein: the providing step is carried out with thedistal portion extending at least 10 cm from a distal end and theproximal portion extending within 40 cm from the distal end or closer.80. The method of claim 78, wherein: the proximal portion has astiffness which is at least 40 times stiffer than the proximal portion.81. The method of claim 78, wherein: the proximal portion has astiffness which is at least 60 times stiffer than the proximal portion.82. The method of claim 77, wherein: the providing step is carried outwith the lumen along the proximal portion having an inner diameter of0.070 to 0.100 inch.
 83. The method of claim 77, wherein: the advancingstep is carried out with the distal portion being advanced throughvessels having a size of less than 4 mm.
 84. A method of forming acatheter, comprising the steps of: providing a liner layer; wrapping areinforcing layer over the liner; positioning a jacket over thereinforcing layer, the jacket having a plurality of jacket sectionsincreasing in flexural modulus at least 25 times from a distal sectionto a proximal section.
 85. The method of claim 83, wherein: thepositioning step is carried out with the jacket sections increasing inflexural modulus at least 40 times.
 86. The method of claim 83, wherein:the positioning step is carried out with increase in flexural modulusoccurring over a length of at least 15 cm.